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Biomedical subjects

J E Valeski

Publications and source records attributed to J E Valeski.

18 recordsLinked to original sources
PubMed2000

Structural alterations in the rat kidney after acute arsine exposure.

The mechanism of arsine (AsH3) toxicity is not completely understood. In this investigation, the toxicity of AsH3 and AsH3-produced hemolytic products was determined in primary culture of renal cortical epithelial cells and in the in situ isolated rat kidney. The objective of this study was to model kidney dysfunction caused by AsH3 exposure. The hypothesis was that unchanged AsH3 and AsH3-produced hemolysate that may contain arsenite (As(III)) as metabolite are both responsible for renal toxicity. Toxicity in isolated cells was determined by 2, 3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxa nilide inner salt (XTT) bioreduction, intracellular potassium (K+), and lactate dehydrogenase (LDH) leakage. Data from XTT bioreduction showed that most toxicity occurred at 1 hour and was independent of the arsenic species. At 4 hours, the observed toxicity depended on the arsenic species and was generated by As(III). In the isolated cells, the As(III)-spiked hemolysate produced similar toxicities with regard to intracellular K and LDH. The AsH3-hemolysate only affected LDH at 1 hour. Unchanged AsH3 was very toxic to the isolated rat kidney. In this system, after 10 minutes exposure to AsH3, the effects of toxicity were observed mainly in the glomerular and peritubular endothelial cells. Tubular epithelial cells also presented early signs of toxicity. The AsH3-hemolysate was not toxic after a 1 -minute exposure. These data suggested that early cytotoxicity caused by unchanged AsH3 results in kidney dysfunction, produced by AsH3, and later by the formation of a hemolysate that may contain As(III). These data may be important in understanding the renal toxic effects after AsH3 intoxication.

Animals↗
PubMed1999

Effect of early transient adherent leukocytes on venular permeability and endothelial actin cytoskeleton.

In a time course study of the development and recovery of venular leaks, it was shown that, after as early as 3 min of histamine application, venular leak formation was identified [Baldwin, A. L., and G. Thurston. Am. J. Physiol. 269 (Heart Circ. Physiol. 38): H1528-H1537, 1995]. This was accompanied by changes in the endothelial actin cytoskeleton and the presence of adherent leukocytes. The venular leaks remained elevated for at least 30 min, whereas the adherent leukocytes were decreased by 20 min. The present study was performed to determine the role that 3 min (early), transient histamine-associated adherent leukocytes play in the formation of venular leaks and changes in the endothelial actin cytoskeleton. In anesthetized rats, the microvasculature of a mesenteric window was perfused with buffered saline or fucoidin. FITC-BSA or FITC-BSA and 10(-4) M histamine was added to the perfusate for the last 3 min. The vasculature was perfusion fixed, stained for filamentous actin, and viewed microscopically. Fucoidin pretreatment significantly reduced the number of early, transient histamine-associated adherent leukocytes (P < 0.01). The number of adherent leukocytes in leaky venules was significantly greater than that seen in nonleaky venules (P < 0.01); however, the reduction in the number of histamine-associated adherent leukocytes with fucoidin pretreatment had no significant effect on the number (P > 0.05) or area (P > 0.05) of FITC-BSA leaks or on the endothelial actin cytoskeleton.

Actins↗
PubMed1998

Ultrastructural effects of intravascularly injected polyethylene glycol-hemoglobin in intestinal mucosa.

Polyethylene glycol (PEG)-conjugated Hb (PEG-Hb) is being considered as a blood substitute. Previously, we showed that PEG-Hb extravasates rapidly from the intestinal mucosa and causes transient epithelial sloughing, resulting in temporary unimpeded passage of material between the intestinal lumen and the microcirculation. The present study quantifies the time course of factors related to this disturbance. Anesthetized Sprague-Dawley rats (350-450 g) were injected with a bolus of PEG-Hb (10 mg/ml) in saline. Control animals received saline, alone or with Dextran 70 (5 mg/ml). After 2, 8, 15, 60, or 90 min, the small intestine was perfusion fixed for microscopy (4 animals for each time point). Epithelial cell detachment and mucosal mast cell degranulation peaked at 2 and 8-15 min, respectively, but by 90 min were back to normal. Goblet cell secretion increased with time up to 8-15 min, after which it leveled off. Mean interstitial width was significantly greater 8 min after injection than for controls and continued to increase with time. In capillaries, endothelial fenestral diaphragms were replaced by thick, amorphous structures. Mesenteric mast cell degranulation was significantly greater 60-90 min after injection compared with controls. We propose that these results are consistent with intravascular injection of PEG-Hb invoking a transient inflammatory response in the intestine.

Animals↗
PubMed1996

Significance of IgG-subclass antibody determinations in bullous pemphigoid.

The presence of circulating basement membrane zone (BMZ) antibodies is characteristic of patients with bullous pemphigoid (BP) and are routinely employed in making the diagnosis. The positive tests, however, occur in 50-70% of patients with BP, thus necessitating consideration of other tests in a significant number of patients. The purpose of this study was to examine the efficacy of indirect immunofluorescence (IF) tests specific for various IgG subclasses antibodies to BMZ in BP, especially in patients who are seronegative on routine indirect IF tests with fluorescein-conjugated antibodies to IgG. BMZ antibodies primarily are of IgG4 subclass and are present in all BMZ antibody positive BP cases. Of BP patients negative for BMZ antibodies, 72% were found positive when tested for IgG4 subclass antibodies. In conclusion, testing for IgG4 subclass BMZ antibodies enhances the sensitivity of serum tests from 68.5% to 91%. This may be due in part to the inherent increased sensitivity of the assay and for detecting subclasses of IgG and in part, due to the subclass distribution of the BP antibodies.

Antibodies↗
PubMed1996

Celiac disease and hypoparathyroidism: cross-reaction of endomysial antibodies with parathyroid tissue.

Celiac disease (CD) is a gluten-sensitive enteropathy characterized by the presence of serum antibodies to endomysial reticulin and gliadin antigens. CD has been associated with various autoimmune endocrine disorders, such as diabetes. We report a rare case of idiopathic hypoparathyroidism with coexistent CD characterized by the presence of serum autoantibodies. Studies were conducted to determine the specificities of these autoantibodies and to localize the antibody binding sites by indirect immunofluorescence and immunoelectron microscopy. Sera from a patient with idiopathic hypoparathyroidism and CD and from two patients with CD alone were tested by indirect immunofluorescence for autoantibodies to parathyroid and endomysial antigens. The specificities of the antibody reactions were determined by testing the sera before and after absorption with monkey stomach tissue. In addition, immunoelectron microscopic studies were performed to determine the localization of the endomysial antigen. Indirect-immunofluorescence studies on the patient's serum were positive with the parathyroid as well as the endomysial substrate. Similar reactions were also observed with the sera of endomysial antibody-positive patients with CD. Absorption of the sera with monkey stomach powder, which is known to have the endomysial antigen, abolished the antibody activities on both the endomysial substrate and the parathyroid tissue. Immunoelectron microscopic studies showed that endomysial antibody activity was associated with antigens localized on the myocyte plasma membrane and in the intercellular spaces. Thus, reactions of the patient's serum with the parathyroid tissue were due to endomysial antibodies and were not parathyroid specific as in patients with idiopathic hypoparathyroidism who did not have coexistent CD. In conclusion, indirect-immunofluorescence tests on parathyroid tissue detect not only tissue-specific antibodies but also cross-reactive antibodies, and this should be taken into consideration when these tests are performed.

Autoantibodies↗
PubMed1992

A characteristic cutaneous direct immunofluorescent pattern associated with Ro(SS-A) antibodies in subacute cutaneous lupus erythematosus.

BACKGROUND: Antibodies to Ro(SS-A) are present in most patients with subacute cutaneous lupus erythematosus (SCLE). Patients with SCLE also have cutaneous immune deposits. However, no correlation of Ro(SS-A) antibodies with immune deposits in skin biopsy specimens has been described. OBJECTIVE: The purpose of this study is to describe characteristic direct immunofluorescence (IF) findings in 32 patients and their association with serum antibodies and clinical diagnosis. METHODS: Serum from patients with characteristic cutaneous direct IF findings was examined for antinuclear antibodies by indirect IF and for antibodies to ribonucleoprotein, Sm, Ro(SS-A), and La(SS-B) by gel immunodiffusion. RESULTS: Twenty-two of 32 patients who exhibited discrete speckled IgG staining predominantly, but not exclusively, of the basal cell cytoplasm had SCLE. Ro(SS-A) antibodies were identified in 23 of 26 patients and Ro(SS-A) and/or La(SS-B) in 25 of 26 patients. CONCLUSION: Direct IF staining characterized by discrete speckled IgG deposits in the basal cell cytoplasm is associated with Ro(SS-A) antibodies and SCLE.

Acute Disease↗
PubMed1992

Differentiation of bullous pemphigoid from epidermolysis bullosa acquisita on frozen skin biopsies.

Patients with bullous pemphigoid and epidermolysis bullosa acquisita may have similar clinical, histologic, and routine immunohistologic features. These two diseases can be distinguished by routine diagnostic studies either on a patient's serum tested by indirect immunofluorescence on salt-split normal skin or by obtaining a fresh perilesional skin biopsy, inducing a split at the lamina lucida, and testing for the site of IgG deposition by direct immunofluorescence. Often the serum studies are negative, while direct immunofluorescent studies yield the characteristic linear IgG staining of the basement membrane zone. To eliminate the need for a repeat biopsy to make a laboratory differential diagnosis, we studied the efficacy of salt-splitting perilesional skin biopsies that had been previously submitted and frozen for routine direct immunofluorescent studies. The biopsies were thawed, salt-split, and processed for direct immunofluorescence. Three epidermolysis bullosa acquisita biopsies and seven bullous pemphigoid biopsies examined demonstrated IgG staining at sites consistent with their respective diagnoses. The IgG appeared in the dermal side of the split biopsies in epidermolysis bullosa acquisita and predominantly, or exclusively, in the epidermal side in bullous pemphigoid. Thus the direct immunofluorescent study of previously frozen and subsequently salt-split skin biopsies may be used for the differential diagnosis of bullous pemphigoid from epidermolysis bullosa acquisita. In most cases, it may eliminate the need for a repeat biopsy.

Basement Membrane↗
PubMed1990

Immunology of celiac disease: tissue and species specificity of endomysial and reticulin antibodies.

Patients with celiac disease and dermatitis herpetiformis have circulating antibodies to reticulin and endomysium, the 'extracellular matrix' components as defined by their detection on rodent and primate tissues, respectively. Because both types of antibodies occur in both forms of gluten-sensitive enteropathy, studies were conducted to determine if the two types of antibodies can be distinguished by species and organ specificity. The results of these studies indicate that distinct endomysium-specific and reticulin-specific antibodies can be found and that these differ in their species specificity; i.e., endomysium antigen occurs in primate and not in rodent tissues while the reticulin antigen occurs in rodent and not in primate tissues. However, the activity of both endomysium and reticulin antibodies demonstrates similar tissue distribution, in that both react to antigens associated with gastrointestinal smooth muscles, peritubular and periglomerular areas of the kidney, and sinusoidal and periportal areas of the liver. Also, both antigens seem to be present in sheep and goat tissue. These studies indicate that the antigens reactive with endomysial antibodies are distinct from those reactive with reticulin antibodies.

Animals↗
PubMed1987

Reticulin and endomysial antibodies in bullous diseases. Comparison of specificity and sensitivity.

Reticulin antibodies of IgG- and IgA-class and endomysial antibodies, which are of the IgA class, were studied by indirect immunofluorescence in 30 normal subjects, and in 45 patients with dermatitis herpetiformis (DH), 31 with pemphigoid, and 30 with pemphigus. Endomysial antibodies were present in 65% of patients with DH maintained on a normal diet and were absent in those on a gluten-free diet and in those with other diseases and in normal controls. Reticulin antibodies of the IgA class were disease specific for DH and occurred in only 25% of such patients. IgG-class reticulin antibodies, on the other hand, were not specific for DH, as they occurred in similar frequencies in patients with pemphigoid and pemphigus and in normal subjects. IgA-class reticulin antibodies occurred primarily in those patients with DH who had high titers of endomysial antibodies. None of the 20 such patients who were negative for endomysial antibodies had IgA-class reticulin antibodies. These studies indicate the high degree of specificity and sensitivity of endomysial antibodies.

Dermatitis Herpetiformis↗
PubMed1981

Test for C3 nephritic factor activity by immunofixation electrophoresis.

This report describes a relatively simple test for C3 nephritic factor (C3NeF) activity utilizing immunofixation electrophoresis to quantitate the production of the breakdown product C3c. Tests performed on plasmas from 22 control patients and 93 renal patients have biopsy diagnoses other than basement membrane dense deposit disease (BMDDD) yielded negative results for C3NeF activity. Tests performed on plasmas from three patients with BMDDD were positive for C3NeF activity, yielding values significantly higher than those for the control group and the patients with other renal diseases. The test can be performed on specimens collected in EDTA to prevent in vitro C3 degradation during storage or transport at ambient temperature.

Basement Membrane↗
PubMed1981

Variability of anti-GBM binding in hereditary nephritis.

Anti-GBM staining by indirect immunofluorescence microscopy was performed on renal biopsies from 64 patients with a variety of diseases in which no in vivo bound immunoglobulin or complement components were identified by direct immunofluorescence microscopy. The glomeruli of all of the entities examined bound anti-GBM antibodies except for four of nine cases of hereditary nephritis of the Alport-type. The absence of anti-GBM staining was found to correlate with the severity of GBM splitting identified by electron microscopy.

Adolescent↗
PubMed1979

Skeletal muscle in polymyositis. Immunohistochemical study.

Thirty-two patients with adult-onset polymyositis uncomplicated by cancer or systemic connective tissue disease were studied. Muscle biopsy specimens were examined with direct immunofluorescence microscopy and results were compared with those in 94 control subjects. Sarcolemmal and sarcoplasmic staining were observed in both groups and considered to be nonspecific. Immune deposits in the muscle microvasculature were present in some cases of systemic lupus erythematosus and dermatomyositis but were not present in polymyositis. Our data suggest that the finding of vascular immunofluorescence excludes the diagnosis of adult polymyositis and implies that the pathogenesis of this disease and other idiopathic inflammatory myopathies may differ.

Adult↗
PubMed1977

Leukemic reticuloendotheliosis: "hairy cell leukemia," functional and structural features of the abnormal cell in a patient with profound leukocytosis.

The development of profound leukocytosis in a patient with leukemic reticuloendotheliosis (LRE) enabled us to obtain purified LRE cells for the investigation of their structural and functional characteristics. The LRE cells of our patient bore surface immunoglobulin and had complement receptors but did not bear Fc receptors and did not form rosettes with sheep erythrocytes. By electron microscopy, the cells were observed to contain typical ribosome lamella structures and to phagocytize both 0.81 micron latex particles and complement-coated zymosan particles. They were adherent to both glass and nylon wool fibers. The mitogenic response to erythroagglutinating phytohemagglutinin was normal to magnitude but delayed chronologically. The binding of 125I-labeled plant lectins was used to characterize the surface topography of LRE cells. Results of these studies indicated that the LRE cell surface differed significantly from the surface of normal T and B lymphocytes and chronic lymphatic leukemia cells. The LRE cells were capable of both stimulating and responding in a one-way mixed lymphocyte culture. However, the LRE cells were not active as effector cells of either cell-mediated lympholysis, a T cell function, or antibody-dependent cellular cytotoxicity, a null cell function. In contrast, they were effector cells of lectin-induced cellular cytotoxicity showing that they did possess the capacity to function as cytotoxic effector cells. These data indicated that the LRE cells in our patient had surface and functional characteristics of both lymphocytes and monocytes.

Binding Sites↗
PubMedDate not supplied

Endomysial antibodies in the diagnosis of celiac disease and the effect of gluten on antibody titers.

Celiac disease, a common chronic gastrointestinal disorder, is gluten induced and is controlled with a gluten-free diet. While the management of CD with a gluten-free diet is quite effective, the diagnosis is rather difficult. The ESPGAN criteria for the diagnosis of CD seems to be tedious and time-consuming. Serological tests for IgA class endomysial antibodies, as detected by indirect immunofluorescence, on human and primate smooth muscles are specific and sensitive markers of celiac disease. Of all the specimens examined, endomysial antibodies were present in patients with gluten-sensitive enteropathy. These antibodies occurred in all active cases of celiac disease, in 90 percent suspected celiac patients where all the ESPGAN criteria has not been fulfilled. This contrasts to the presence of endomysial antibodies in 46 percent of confirmed and 17 percent of suspected celiac patients maintained on a gluten-free diet for various time intervals. Endomysial antibodies also occurred in all cases with chronic diarrhea and gut histology consistent with CD and 8% of asymptomatic family members of CD patients. None of the patients with other gastrointestinal and liver diseases had endomysial antibodies. These studies thus emphasize the specificity and sensitivity of endomysial antibodies for celiac disease.

Animals↗